A broadly conserved fungal chorismate mutase targets the plant shikimate pathway to regulate salicylic acid production and other secondary metabolites

The molecular dynamics of plant-pathogen interactions are complex, involving a constant defense race between host plants and pathogens. Plants deploy antimicrobial metabolites and physiological responses to inhibit pathogens, while pathogens counteract these defenses using secreted proteinaceous effectors. Chorismate mutases (CMs) are effectors largely studied in biotrophic fungi and nematodes for their ability to hijack the host shikimate pathway by diverting chorismate from salicylic acid (SA) biosynthesis, subsequently undermining SA-mediated defenses against biotrophic infection. While CMs have been primarily linked to biotrophy, we identified a novel bifunctional CM from the broad host range and predominantly necrotrophic pathogen Sclerotinia sclerotiorum and demonstrate that orthologs of this secreted CM are present in far more diverse fungal lifestyles than initially theorized. Unlike currently characterized secreted CMs, S. sclerotiorum CM (SsCM1) localizes to the plant chloroplast where it interacts with plant plastidic CMs. While SsCM1 is a functional, albeit weak CM, it contains a novel domain architecture of bacterial origin, including a putative isochorismate pyruvate lyase (IPL) domain. Interestingly, transient expression of SsCM1 in planta increases rather than decreases host SA levels. Our results indicate that secreted CMs are broadly conserved in many plant-associating fungi beyond canonical biotrophs and likely facilitate infection through a novel manipulation of the plant shikimate pathway that redirects the flow of this pathway toward increased SA production and away from the biosynthesis of downstream antimicrobial compounds. We propose that SsCM1-like effectors represent a novel class of secreted CMs that may be commonly utilized by plant-associated necrotrophs to achieve pathogenic success. IMPORTANCE Microbial effectors are small secreted proteins that help pathogens establish disease within the host environment. In biotrophic fungi, secreted chorismate mutases (CMs) like Cmu1 suppress the production of salicylic acid (SA), a key plant hormone involved in resistance against biotrophic pathogens. Since Cmu1 and its homologs are exclusively found in biotrophic pathogens, secreted CMs have been considered a hallmark of biotrophy. Surprisingly, we identified a secreted CM, encoded by SsCM1, in the predominantly necrotrophic fungus Sclerotinia sclerotiorum. Structural and functional studies suggest SsCM1 is likely a functional homolog acquired from bacteria and specifically acts to suppress the production of antimicrobial compounds that would otherwise enhance plant resistance to necrotrophs. Unlike Cmu1, SsCM1 localizes to plastids, inversely regulates SA, and is conserved more broadly across the fungal kingdom. Thus, our findings reveal a new branch of plastid-localized CMs in necrotrophs, offering new avenues for the development of potential broad-spectrum antimicrobial treatments targeting this pathogen group.